1. Field of the Invention:
This invention relates to a process for preparing a ketocholanate comprising oxidizing a cholanate which has a protected hydroxyl group at the 3-position and hydroxyl group(s) at the 12-position and optionally at the 7-position with an alkali metal salt of an oxo acid of halogen in the presence of a cerium compound.
2. Description of the Prior Art:
Ketocholanic acid and its derivatives are known to be effective in accelerating the absorption of fat-soluble vitamins and the secretion of bile as well as in treating various hepatic disorders. Further these compounds are important as intermediates in the synthesis of dehydrocholic acid or chenodeoxycholic acid.
There have been reported a number of processes for the oxidation of cholanic acid derivatives having hydroxyl group(s).
For example, French Pat. No. 854817 has disclosed a process for preparing 7-keto-3.alpha., 12.alpha.,-dihydroxycholanic acid by adding an equimolar amount of bromine to an aqueous solution of cholic acid and sodium bicarbonate to thereby selectively oxidize the cholic acid. U.S. Pat. No. 2576728 has disclosed a process for preparing 3,7,12-triketocholanic acid by selectively and completely oxidizing 7-keto-3.alpha., 12.alpha.-dihydroxycholanic acid in an aqueous solution of a mixture of sodium hydroxide, sodium bicarbonate and sodium bromide at a low temperature with the use of chlorine gas. Japanese Patent Publication No. 20493/ 1970 has disclosed a process for preparing keto bile acids by oxidizing bile acids having hydroxyl group(s) with antiformin in the presence of an alkali metal acetate. However each of these known processes has some disadvantages such as a poor yield and/or a low purity of the desired product or a prolonged reaction time and thus is unsatisfactory from the practical viewpoint.
Therefore there has been generally employed a process for oxidizing cholanic acid which comprises first esterifying a carboxylic acid with an alcohol, protecting, if necessary, the hydroxyl group(s) not to be converted into keto group(s) by, for example, acylation, and then oxidizing the product.
It is known that a heavy metal oxidizing agent such as chromic acid, potassium chromate or sodium bichromate is employed in the above oxidation. Thus this process is accompanied by some disadvantages such that the waste water thereof contains toxic chromium compound(s) and that the product per se may be contaminated with the same. Accordingly there have been proposed processes wherein no heavy metal oxidizing agent is used. Examples of these processes include one wherein cholic acid is oxidized in a solvent mixture comprising a fatty acid and an alcohol with an aqueous alkaline solution of sodium hypochlorite (cf. Japanese Patent Laid-Open No. 51259/1974); and another one wherein the oxidation is carried out in a nonaqueous solvent with the use of bromocarbamide (cf. Japanese Patent Publication No. 41420/1981).
However each of these processes has some disadvantages such as a poor yield and/or a low purity of the desired product or a prolonged reaction time. Thus it has been required to improve the same.